Users of Plavix, Valium, Other Meds Could Suffer Reactions if they Carry CYP2C19 Gene Variant

Does a gene variant explain a U.S. lawmaker’s odd behavior? According to Rep. David Wu, an Oregon Democrat, a variant in the CYP2C19 gene, which plays a role in metabolizing some drugs, like Plavix and Valium was the reason he seemingly went AWOL around Election Day in 2008.

We’ve written about the CYP2C19 gene variant before. People with the type of gene variant Wu described are slow metabolizers of the anti-blood clotting drug Plavix, making it less effective for them. Heartburn drugs called proton pump inhibitors (Prilosec, Nexium, etc.) are also known to inhibit this gene, raising questions as to whether people taking Plavix should use such drugs.

The Plavix issue was serious enough to prompt the U.S. Food & Drug Administration (FDA) to order that the drug bear a boxed warning indicating that patients with diminished CYP2C19 function are at greater risk of cardiovascular adverse events after an acute coronary syndrome or percutaneous coronary intervention than normal metabolizers of Plavix. According to the labeling language, it is up to doctors to determine when they should genetically test patients before Plavix administration. They may choose to wait to see how patients react to a particular dose of Plavix and then decide whether to switch to another drug depending on the outcome.

Rep. Wu recently told OregonLive.com that a CYP2C19 variant caused him to suffer a strange reaction to Valium and Ambien in 2008 that required emergency hospitalization, and this accounts for his being missing in action at the time. According to Wu, CYP2C19 caused his body to improperly metabolize the Valium.

According to OregonLive.com, the CYP2C19 gene variant is more common in people of Asian descent. But it does affect other ethnicities as well, including fewer than 5 percent of Caucasians and African-Americans. But simply carrying the gene variant isn’t a good predictor that an individual will not be able to metabolize a drug. One study of Han Chinese – an ethnic group in which the gene variant affects roughly 40 percent of the population – only 20 percent turned out to be slow metabolizers.

According to the DNA testing firm Genelex, CYP2C19 acts on 5-10 percent of drugs in current clinical use. Genetic testing can look for common changes CYP2C19 gene to determine if an individual may have difficulty metabolizing a drug. While this may help doctors choose the best drug and dose for an individual with less trial and error, it’s not clear how worthwhile such testing is. What studies have been done on this type of testing have failed to find a clear benefit.